126 replies to this topic

[Blue]

OBJECTIVE: We have evaluated the effects on mortality of habitual low carbohydrate-high-protein diets that are thought to contribute to weight control. DESIGN: Cohort investigation. SETTING: Adult Greek population. SUBJECTS METHODS: Follow-up was performed from 1993 to 2003 in the context of the Greek component of the European Prospective Investigation into Cancer and nutrition. Participants were 22 944 healthy adults, whose diet was assessed through a validated questionnaire. Participants were distributed by increasing deciles according to protein intake or carbohydrate intake, as well as by an additive score generated by increasing decile intake of protein and decreasing decile intake of carbohydrates. Proportional hazards regression was used to assess the relation between high protein, high carbohydrate and the low carbohydrate-high protein score on the one hand and mortality on the other. RESULTS: During 113 230 persons years of follow-up, there were 455 deaths. In models with energy adjustment, higher intake of carbohydrates was associated with significant reduction of total mortality, whereas higher intake of protein was associated with nonsignificant increase of total mortality (per decile, mortality ratios 0.94 with 95% CI 0.89 -0.99, and 1.02 with 95% CI 0.98 -1.07 respectively). Even more predictive of higher mortality were high values of the additive low carbohydrate-high protein score (per 5 units, mortality ratio 1.22 with 95% CI 1.09 -to 1.36). Positive associations of this score were noted with respect to both cardiovascular and cancer mortality. CONCLUSION: Prolonged consumption of diets low in carbohydrates and high in protein is associated with an increase in total mortality.
http://www.ncbi.nlm....pubmed/17136037

[Blue]

OBJECTIVE: The long-term health consequences of diets used for weight control are not established. We have evaluated the association of the frequently recommended low carbohydrate diets - usually characterized by concomitant increase in protein intake - with long-term mortality. DESIGN: The Women's Lifestyle and Health cohort study initiated in Sweden during 1991-1992, with a 12-year almost complete follow up. SETTING: The Uppsala Health Care Region. SUBJECTS: 42,237 women, 30-49 years old at baseline, volunteers from a random sample, who completed an extensive questionnaire and were traced through linkages to national registries until 2003. MAIN OUTCOME MEASURES: We evaluated the association of mortality with: decreasing carbohydrate intake (in deciles); increasing protein intake (in deciles) and an additive combination of these variables (low carbohydrate-high protein score from 2 to 20), in Cox models controlling for energy intake, saturated fat intake and several nondietary covariates. RESULTS: Decreasing carbohydrate or increasing protein intake by one decile were associated with increase in total mortality by 6% (95% CI: 0-12%) and 2% (95% CI: -1 to 5%), respectively. For cardiovascular mortality, amongst women 40-49 years old at enrolment, the corresponding increases were, respectively, 13% (95% CI: -4 to 32%) and 16% (95% CI: 5-29%), with the additive score being even more predictive. CONCLUSIONS: A diet characterized by low carbohydrate and high protein intake was associated with increased total and particularly cardiovascular mortality amongst women. Vigilance with respect to long-term adherence to such weight control regimes is advisable.
http://www.ncbi.nlm....pubmed/17391111

[Skötkonung]

Positive associations of this score were noted with respect to both cardiovascular and cancer mortality. CONCLUSION: Prolonged consumption of diets low in carbohydrates and high in protein is associated with an increase in total mortality.
http://www.ncbi.nlm....pubmed/17136037

This doesn't make sense to me, perhaps you can explain:

Effects of a ketogenic diet on tumor metabolism and nutritional status in pediatric oncology patients: two case reports
"RESULTS: Within 7 days of initiating the ketogenic diet, blood glucose levels declined to low-normal levels and blood ketones were elevated twenty to thirty fold. Results of PET scans indicated a 21.8% average decrease in glucose uptake at the tumor site in both subjects. One patient exhibited significant clinical improvements in mood and new skill development during the study. She continued the ketogenic diet for an additional twelve months, remaining free of disease progression. CONCLUSION: While this diet does not replace conventional antineoplastic treatments, these preliminary results suggest a potential for clinical application which merits further research. "

Growth of human gastric cancer cells in nude mice is delayed by a ketogenic diet supplemented with omega-3 fatty acids and medium-chain triglycerides
"Application of an unrestricted ketogenic diet enriched with omega-3 fatty acids and MCT delayed tumour growth in a mouse xenograft model. Further studies are needed to address the impact of this diet on other tumour-relevant functions such as invasive growth and metastasis."

Carbohydrate restriction in patients with advanced cancer: a protocol to assess safety and feasibility with an accompanying hypothesis
"We are exploring the potential of carbohydrate restriction to inhibit cancer growth in susceptible patients. We have presented the protocol for our ongoing clinical feasibility trial, analogous to a phase I drug trial, and a synopsis of the motivating hypothesis. Our hypothesis leads us to speculate that a VLCK diet may stabilize tumor progression or lead to improvement in up to two-thirds of our subjects."

The calorically restricted ketogenic diet, an effective alternative therapy for malignant brain cancer
"The results indicate that KetoCal^® has anti-tumor and anti-angiogenic effects in experimental mouse and human brain tumors when administered in restricted amounts. The therapeutic effect of KetoCal^® for brain cancer management was due largely to the reduction of total caloric content, which reduces circulating glucose required for rapid tumor growth. A dependency on glucose for energy together with defects in ketone body metabolism largely account for why the brain tumors grow minimally on either a ketogenic-restricted diet or on a standard-restricted diet. Genes for ketone body metabolism should be useful for screening brain tumors that could be targeted with calorically restricted high fat/low carbohydrate ketogenic diets. This preclinical study indicates that restricted KetoCal^® is a safe and effective diet therapy and should be considered as an alternative therapeutic option for malignant brain cancer."

I think the mechanism here can be described by the Warburg effect.

"In oncology, the Warburg effect is the observation that most cancer cells predominantly produce energy by glycolysis followed by lactic acid fermentation in the cytosol, rather than by oxidation of pyruvate in mitochondria like most normal cells.^[1] This occurs even if oxygen is plentiful. Otto Warburg postulated that this change in metabolism is the fundamental cause of cancer,^[2] a claim now known as the Warburg hypothesis. Today it is known that mutations in oncogenes and tumor suppressor genes are the fundamental cause of cancer.^[3][4] The Warburg effect may simply be a consequence of damage to the mitochondria in cancer, or an adaptation to low-oxygen environments within tumors, or a result of cancer genes shutting down the mitochondria because they are involved in the cell's apoptosis program which would otherwise kill cancerous cells."

[Blue]

Extremely few people have a diet with so little carbohydrates and protein that they achieve long-term ketosis. So studies regarding a true ketogenic diet, that is producing ketone bodies and not wrongly "ketogenic diet"=reduced carbohydrates, are not relevant for the epidemiological studies.

[Skötkonung]

OBJECTIVE: The long-term health consequences of diets used for weight control are not established. We have evaluated the association of the frequently recommended low carbohydrate diets - usually characterized by concomitant increase in protein intake - with long-term mortality. DESIGN: The Women's Lifestyle and Health cohort study initiated in Sweden during 1991-1992, with a 12-year almost complete follow up. SETTING: The Uppsala Health Care Region. SUBJECTS: 42,237 women, 30-49 years old at baseline, volunteers from a random sample, who completed an extensive questionnaire and were traced through linkages to national registries until 2003. MAIN OUTCOME MEASURES: We evaluated the association of mortality with: decreasing carbohydrate intake (in deciles); increasing protein intake (in deciles) and an additive combination of these variables (low carbohydrate-high protein score from 2 to 20), in Cox models controlling for energy intake, saturated fat intake and several nondietary covariates. RESULTS: Decreasing carbohydrate or increasing protein intake by one decile were associated with increase in total mortality by 6% (95% CI: 0-12%) and 2% (95% CI: -1 to 5%), respectively. For cardiovascular mortality, amongst women 40-49 years old at enrolment, the corresponding increases were, respectively, 13% (95% CI: -4 to 32%) and 16% (95% CI: 5-29%), with the additive score being even more predictive. CONCLUSIONS: A diet characterized by low carbohydrate and high protein intake was associated with increased total and particularly cardiovascular mortality amongst women. Vigilance with respect to long-term adherence to such weight control regimes is advisable.
http://www.ncbi.nlm....pubmed/17391111

Basically the results of that study are worthless as far as having any predictability to the longevity effects of low-carb diets for a couple of reasons. First, it's an epidemiological study, which can't show causality. Second, the relation between carbs and protein and longevity are within a range of protein and (especially) carbs that are not found in low-carb diets and, therefore, can't be extrapolated to them.

Furthermore, both of those studies are contradicted here:
Low-Carbohydrate-Diet Score and the Risk of Coronary Heart Disease in Women
"Results During 20 years of follow-up, we documented 1994 new cases of coronary heart disease. After multivariate adjustment, the relative risk of coronary heart disease comparing highest and lowest deciles of the low-carbohydrate-diet score was 0.94 (95% confidence interval [CI], 0.76 to 1.18; P for trend=0.19). The relative risk comparing highest and lowest deciles of a low-carbohydrate-diet score on the basis of the percentage of energy from carbohydrate, animal protein, and animal fat was 0.94 (95% CI, 0.74 to 1.19; P for trend=0.52), whereas the relative risk on the basis of the percentage of energy from intake of carbohydrates, vegetable protein, and vegetable fat was 0.70 (95% CI, 0.56 to 0.88; P for trend=0.002). A higher glycemic load was strongly associated with an increased risk of coronary heart disease (relative risk comparing highest and lowest deciles, 1.90; 95% CI, 1.15 to 3.15; P for trend=0.003). Conclusions Our findings suggest that diets lower in carbohydrate and higher in protein and fat are not associated with increased risk of coronary heart disease in women. When vegetable sources of fat and protein are chosen, these diets may moderately reduce the risk of coronary heart disease."

Here is an analysis in the context of the Nurses Health Study, with a total of more than 82,000 respondents who every two years filled out a questionnaire about their food intake and were followed for a period of twenty years. The results suggested that there was no correlation between low carbohydrate intake and cardiovascular disease and that if vegetable sources of protein and fat were consumed, a negative correlation occured. There was, by contrast, a mild link between total carbohydrate intake and coronary heart disease and a strong link if this food contained a high glycemic load.

Edited by Skotkonung, 20 October 2009 - 07:04 PM.

[Skötkonung]

Extremely few people have a diet with so little carbohydrates and protein that they achieve long-term ketosis. So studies regarding a true ketogenic diet, that is producing ketone bodies and not wrongly "ketogenic diet"=reduced carbohydrates, are not relevant for the epidemiological studies.

Most ketogenic diet protocols require sub 50g carbohydrate daily. I am not aware of a 150g carbohydrate diet (a reduced carbohydrate diet by most standards) being classified under ketogenic in any scientific nomenclature. Do you have sources?

[Blue]

Furthermore, both of those studies are contradicted here:
Low-Carbohydrate-Diet Score and the Risk of Coronary Heart Disease in Women
"Results During 20 years of follow-up, we documented 1994 new cases of coronary heart disease. After multivariate adjustment, the relative risk of coronary heart disease comparing highest and lowest deciles of the low-carbohydrate-diet score was 0.94 (95% confidence interval [CI], 0.76 to 1.18; P for trend=0.19). The relative risk comparing highest and lowest deciles of a low-carbohydrate-diet score on the basis of the percentage of energy from carbohydrate, animal protein, and animal fat was 0.94 (95% CI, 0.74 to 1.19; P for trend=0.52), whereas the relative risk on the basis of the percentage of energy from intake of carbohydrates, vegetable protein, and vegetable fat was 0.70 (95% CI, 0.56 to 0.88; P for trend=0.002). A higher glycemic load was strongly associated with an increased risk of coronary heart disease (relative risk comparing highest and lowest deciles, 1.90; 95% CI, 1.15 to 3.15; P for trend=0.003). Conclusions Our findings suggest that diets lower in carbohydrate and higher in protein and fat are not associated with increased risk of coronary heart disease in women. When vegetable sources of fat and protein are chosen, these diets may moderately reduce the risk of coronary heart disease."

Here is an analysis in the context of the Nurses Health Study, with a total of more than 82,000 respondents who every two years filled out a questionnaire about their food intake and were followed for a period of twenty years. The results suggested that there was no correlation between low carbohydrate intake and cardiovascular disease and that if vegetable sources of protein and fat were consumed, a negative correlation occured. There was, by contrast, a mild link between total carbohydrate intake and coronary heart disease and a strong link if this food contained a high glycemic load.

Interesting But did not look at all-cause or even CVD mortality but only at new cases of one specific form of CVD disease. Also not directly comparable to the other studies in that it looked at composite "score", so calculations were different.

[Blue]

Most ketogenic diet protocols require sub 50g carbohydrate daily.

Do you have a source for that sub 50g carbohydrates and an average or high protein intake will cause ketosis?

Edited by Blue, 20 October 2009 - 07:54 PM.

[HaloTeK]

Blue, Ketosis is less likely to happen as the result of high protein because of glucogenesis.

Once fat intake reaches 75%+ you will really start to see ketones.

Most ketogenic diet protocols require sub 50g carbohydrate daily.

Do you have a source for that sub 50g carbohydrates and an average or high protein intake will cause ketosis?

[Blue]

Blue, Ketosis is less likely to happen as the result of high protein because of glucogenesis.

Once fat intake reaches 75%+ you will really start to see ketones.

Most ketogenic diet protocols require sub 50g carbohydrate daily.

Do you have a source for that sub 50g carbohydrates and an average or high protein intake will cause ketosis?

Yes, I know. My point was that many diets that are called "ketogenic" may not be that at all and are simply somewhat carbohydrate restricted. You cannot look at experimental studies that do induce ketone production and are beneficial for, say, cancer and say that this proves that epidemiological studies finding less cancer from more carbohydrates are incorrect. Extreme diets that cause long-term ketone production are rarely seen among most of today's humans.

[tunt01]

imo:

1. An epidemiological doesn't necessarily delineate causative pathways. there are studies which show higher incidence of ice cream and childhood drownings in lakes/swimming pools during the summer time, but no one is saying if you eat ice cream you are at risk of drowning. what matters is if the study is statistically significant data, and that is what we have here. you can take it at face value or choose to reject it, but it is not a study of metabolic pathways. it is not even suggesting a causative pathway, they typically point to "risk level".

2. Trotting out cancer studies to refute (what I personally think is a long-standing, acknowledged fact) that diets deficient in carbs can lead to cardiovascular problems, seems like comparing apples to oranges. We can point to medical facts which show reducing protein intake is probably one of the most sound diet strategies for people suffering from alzheimers, but that illness doesn't necessarily have complete and direct comparative value to CVD. Why compare metabolic cancer studies on ketosis to refute some papers on CVD/carbs?

Edited by prophets, 20 October 2009 - 09:03 PM.

[kismet]

Acutally, strong, prospective epidemiology is usually preferred to "delineating" pathways, i.e. purely mechanistic in vitro or preclinical animal studies. The latter though necessary, mostly to generate and test hypothesis, is generally weaker evidence than the former from a practical POV. The only study design superior is, obviously, an RCT. The emphasis is on plausible, well-designed, well-controlled and repeated.

So I'm wondering about control here. Protein intake from what sources? Adjusted for vegetable intake and other risk factors?! (energy adjustment only as possibly in the first study is not enough by any stretch of the imagination) Methionine adjusted? I'd like to know more about the second cohort you posted, which seems well-controlled.

Edited by kismet, 20 October 2009 - 10:20 PM.

[Skötkonung]

2. Trotting out cancer studies to refute (what I personally think is a long-standing, acknowledged fact) that diets deficient in carbs can lead to cardiovascular problems, seems like comparing apples to oranges. We can point to medical facts which show reducing protein intake is probably one of the most sound diet strategies for people suffering from alzheimers, but that illness doesn't necessarily have complete and direct comparative value to CVD. Why compare metabolic cancer studies on ketosis to refute some papers on CVD/carbs?

Because the second study indicated elevated risk for cancer as part of the mortality statistics. That is why I quoted that section.

[tunt01]

So I'm wondering about control here. Protein intake from what sources? Adjusted for vegetable intake and other risk factors?! (energy adjustment only as possibly in the first study is not enough by any stretch of the imagination) Methionine adjusted? I'd like to know more about the second cohort you posted, which seems well-controlled.

this is a really good point.

i sometimes feel like we end up going in circles about the same issues in these never-ending diet threads. but this point you mention, is an issue that has been on my mind for sometime and i cannot come to terms with a proper answer one way or another.

there was a rancho bernardo study that might be worth looking at briefly.

http://www.ncbi.nlm....pubmed/11914191

PUBMED ABSTRACT:

The role of dietary protein in osteoporosis is unclear, with previous studies having suggested both protection and harm. The associations of total, animal, and vegetable protein with bone mineral density (BMD) and the variations in these associations with calcium intake were studied in a community-dwelling cohort of 572 women and 388 men aged 55-92 years (Rancho Bernardo, California). Multiple linear regression analyses adjusted for standard osteoporosis covariates showed a positive association between animal protein consumption, assessed by food frequency questionnaires in 1988-1992, and BMD, measured 4 years later. This association was statistically significant in women. For every 15-g/day increase in animal protein intake, BMD increased by 0.016 g/cm2 at the hip (p = 0.005), 0.012 g/cm2 at the femoral neck (p = 0.02), 0.015 g/cm2 at the spine (p = 0.08), and 0.010 g/cm2 for the total body (p = 0.04). Conversely, a negative association between vegetable protein and BMD was observed in both sexes. Some suggestion of effect modification by calcium was seen in women, with increasing protein consumption appearing to be more beneficial for women with lower calcium intakes, but evidence for this interaction was not consistently strong. This study supports a protective role for dietary animal protein in the skeletal health of elderly women.

the data was not statistically significant for men, but trended in the same direction. i'd like to find more good studies on animal vs. plant protein and get a deeper understanding of this issue.

the study cites specifically in its conclusion:

A significant negative association between vegetable protein intake and BMD was observed. While not expected, this result is also not inconsistent with previous work; Munger et al. (14) reported an increase in age-adjusted hip fracture risk with increasing quartile of vegetable protein consumption. In Rancho Bernardo participants, the negative association between vegetable protein and BMD existed despite a positive correlation between vegetable protein and both animal (r = 0.42) and total (r = 0.70) protein consumption.

Differences in the effects of animal and vegetable sources of protein on bone are not simple to predict from the endogenous acid theory; the greater alkaline ash content of vegetable foods should theoretically provide a protective buffering effect, but sulfur-containing amino acid content, which increases the acid load, varies markedly among vegetable foods relative to animal foods (36). Since the associations observed in this and other populations do not generally support a dominant role for the endogenous acid mechanism in bone health, other explanations for the differing effects of animal and vegetable protein should also be considered.

perhaps a lower animal protein/methionine diet is consistent with higher risk for sarcopenia, offset by reduced growth and cancer risk. i'm not firm on what the "ideal diet" is, but it seems like we constantly run into this proverbially trade-off between the benefits/risks and the idea is to strike the right balance. i am currently on a CR-like mediterranean/okinawan diet.

[Skötkonung]

Blue, Ketosis is less likely to happen as the result of high protein because of glucogenesis.

Once fat intake reaches 75%+ you will really start to see ketones.

Most ketogenic diet protocols require sub 50g carbohydrate daily.

Do you have a source for that sub 50g carbohydrates and an average or high protein intake will cause ketosis?

Yes, I know. My point was that many diets that are called "ketogenic" may not be that at all and are simply somewhat carbohydrate restricted. You cannot look at experimental studies that do induce ketone production and are beneficial for, say, cancer and say that this proves that epidemiological studies finding less cancer from more carbohydrates are incorrect. Extreme diets that cause long-term ketone production are rarely seen among most of today's humans.

The Johns Hopkins Hospital protocol for initiating the ketogenic diet is the most widely adopted method of inducing ketosis in clinical settings.

This is the protocol:

TABLE
A protocol for administration of the ketogenic diet. Attached is a study containing that protocol.
 HartmanViningKDReview.pdf   109.38KB   67 downloads

Ketosis is defined by the amount of ketones present in the blood. Ketogenic is an adjective defining a diet that will cause the occurrence of ketosis.

[Skötkonung]

the data was not statistically significant for men, but trended in the same direction. i'd like to find more good studies on animal vs. plant protein and get a deeper understanding of this issue.

Regarding plant and animal proteins in the context of bone health, animal proteins have an acidic PRAL (probably renal acid load) and that if unbalanced, a gradual calcium leaching will occur from the bones. It is thought that balancing foods with an acidic PRAL score with foods that have a alkaline PRAL score will prevent this from occurring. Many western cultures have high rates of osteoporosis, and they also consume high amounts of meat and grains (both acidic PRAL). However, if one eats either grains or meat and proceeds with eating high amounts of vegetables and berries, this problem will not occur. At least that is the theory behind PRAL scores.

In another post, there was a discussion of PRAL scores and it was pointed out to me that it might not be the cause of osteoporosis.

[kismet]

I did not yet see any debunking evidence of the PRAL - bone health or more importantly blood pH - bone hypothesis, did I miss it? Prophet's studies only go to show that the relationships are complex -- as expected.

Edited by kismet, 21 October 2009 - 01:14 PM.

[Blue]

Blue, Ketosis is less likely to happen as the result of high protein because of glucogenesis.

Once fat intake reaches 75%+ you will really start to see ketones.

Most ketogenic diet protocols require sub 50g carbohydrate daily.

Do you have a source for that sub 50g carbohydrates and an average or high protein intake will cause ketosis?

Yes, I know. My point was that many diets that are called "ketogenic" may not be that at all and are simply somewhat carbohydrate restricted. You cannot look at experimental studies that do induce ketone production and are beneficial for, say, cancer and say that this proves that epidemiological studies finding less cancer from more carbohydrates are incorrect. Extreme diets that cause long-term ketone production are rarely seen among most of today's humans.

The Johns Hopkins Hospital protocol for initiating the ketogenic diet is the most widely adopted method of inducing ketosis in clinical settings.

This is the protocol:

TABLE
A protocol for administration of the ketogenic diet. Attached is a study containing that protocol.
 HartmanViningKDReview.pdf   109.38KB   67 downloads

Ketosis is defined by the amount of ketones present in the blood. Ketogenic is an adjective defining a diet that will cause the occurrence of ketosis.

That protocol is certainly not followed by all studies claiming a "ketogenic diet". Here is one:

"At the first visit, participants were instructed how to fol-low the LCKD as individuals or in small groups, with aninitial goal of ≤20 g carbohydrate per day. Participantswere taught the specific types and amounts of foods theycould eat, as well as foods to avoid. Initially, participantswere allowed unlimited amounts of meats, poultry, fish,shellfish, and eggs; 2 cups of salad vegetables per day; 1cup of low-carbohydrate vegetables per day; 4 ounces ofhard cheese; and limited amounts of cream, avocado,olives, and lemon juice. Fats and oils were not restrictedexcept that intake of trans fats was to be minimized."

This study actually measured ketone bodies:
"The proportion ofparticipants with a urine ketone reading greater than tracewas 1 of 17 participants at baseline, 5 of 17 participants atweek 2, and similar frequencies at subsequent visits untilweek 14 when 2 of 18 participants had readings greaterthan trace and week 16 when 2 of 21 participants had readings greater than trace. During the study, only 27 of151 urine ketone measurements were greater than trace,with one participant accounting for all 7 occurrences ofthe highest urine ketone reading."

Despite this the title of the study proudly proclaims that it was a ketogenic diet: "A low-carbohydrate, ketogenic diet to treat type 2 diabetes""!!!
http://srv9.louhi.ne...3-7052-2-34.pdf

Edited by Blue, 21 October 2009 - 03:13 PM.

[Blue]

Here is a meta-analysis refuting the acid -> osteoporosis theory:

"Abstract The acid-ash hypothesis posits that protein and grain foods, with a low potassium intake, produce a diet acid load, net acid excretion (NAE), increased urine calcium, and release of calcium from the skeleton, leading to osteoporosis. The objectives of this meta-analysis were to assess the effect of changes in NAE, by manipulation of healthy adult subjects' acid-base intakes, on urine calcium, calcium balance, and a marker of bone metabolism, N-telopeptides. This meta-analysis was limited to studies that used superior methodological quality for the study of calcium metabolism. We systematically searched the literature and included studies if subjects were randomized to the interventions and followed the recommendations of the Institute of Medicine's Panel on Calcium and Related Nutrients for calcium studies. Results: Five of 16 studies met the inclusion criteria. The studies altered the amount and/or type of protein. Despite a significant linear relationship between an increase in NAE and urinary calcium (p < 0.0001), there was no relationship between a change of NAE and a change of calcium balance (p = 0.38), power = 94%. There was no relationship between a change of NAE and a change in the marker of bone metabolism, N-telopeptides (p = 0.95). In conclusion, this meta-analysis does not support the concept that the calciuria associated with higher NAE reflects a net loss of whole body calcium. There is no evidence from superior quality balance studies that increasing the diet acid load promotes skeletal bone mineral loss or osteoporosis. Changes of urine calcium do not accurately represent calcium balance."
http://www.ncbi.nlm....pubmed/19419322

[Blue]

Basically the results of that study are worthless as far as having any predictability to the longevity effects of low-carb diets for a couple of reasons. First, it's an epidemiological study, which can't show causality. Second, the relation between carbs and protein and longevity are within a range of protein and (especially) carbs that are not found in low-carb diets and, therefore, can't be extrapolated to them.

You are of course right that diets using very low carbohydrates and especially a diet causing ketosis are almost never found in the general population so an epidemiologic study does not cover this extremity. But I do not think there is any study showing the really long-term effects of that diet. Some historic populations such as the Inuits may have had such a diet but their average life expectancy was short so advocates should be wise to dismiss them by claiming lack of modern medical care etc. So anyone doing such diets long-term are taking a leap into the unknown.

[Blue]

perhaps a lower animal protein/methionine diet is consistent with higher risk for sarcopenia, offset by reduced growth and cancer risk. i'm not firm on what the "ideal diet" is, but it seems like we constantly run into this proverbially trade-off between the benefits/risks and the idea is to strike the right balance.

That is what I think could be expected from lowering IGF-1 which PR seems to do. But it is a double-edged sword as mentioned.

Edited by Blue, 21 October 2009 - 03:52 PM.

[Blue]

Two interesting studies:

"BACKGROUND: High-glycemic index diets have been linked to greater risk of cardiovascular disease and type 2 diabetes. Postprandial glycemia within the normal range may promote oxidative stress and inflammatory processes underlying the development of disease. OBJECTIVE: We explored acute differences in the activation of the inflammatory marker nuclear factor-kappaB after consumption of 2 carbohydrate meals matched for macronutrient and micronutrient composition but differing in glycemic index. DESIGN: After an overnight fast, 10 young, lean healthy subjects were fed in random order 3 meals providing 50 g of available carbohydrate as glucose, white bread, or pasta. Venous blood samples were collected at 0, 1, 2, and 3 h, and nuclear proteins were extracted from mononuclear cells. Changes in nuclear factor-kappaB-p65 proteins were detected by Western blotting. Acute changes in other markers of oxidative stress (nitrotyrosine and soluble intercellular adhesion molecule-1) were also assessed. RESULTS: The maximum increase in nuclear factor-kappaB activation was similar after the bread meal [mean (+/-SEM) area under the curve: 69 +/- 16% optical density x h] and the glucose challenge (75 +/- 9% optical density x h), but was 3 times higher than after the pasta meal (23 +/- 5% optical density x h) (P < 0.05). Similarly, changes in nitrotyrosine, but not soluble intercellular adhesion molecule-1, were higher after glucose and bread than after pasta (P = 0.01 at 2 h). CONCLUSIONS: The findings suggest that high-normal physiologic increases in blood glucose after meals aggravate inflammatory processes in lean, young adults. This mechanism may help to explain relations between carbohydrates, glycemic index, and the risk of chronic disease."
http://www.ncbi.nlm....pubmed/18469238

"Abstract The aim was to study the effect of a standardized oral fat load (OFL) on different inflammatory parameters in a large sample of adult healthy subjects (n = 286) of both sexes. The fat load was given between 08:00 and 09:00 h after a 12-h fast. Blood samples were drawn before and 3, 6, 9, and 12 h after the OFL. All patients underwent a measurement of body mass index (BMI), blood glucose (BG), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (Tg), soluble intercellular adhesion molecule-1 (sICAM-1), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin), and tumor necrosis factor-α (TNF-α). Fasting plasma glucose (FPG) increase was +3.26% at 3 h, +4.35% at 6 h, +1.09% at 9 h while FPG decrease was −1.09% at 12 h. High-density lipoprotein cholesterol increase was +2.08% at 3 h, and at 12 h during OFL study; a significant HDL-C decrease was present in subjects after 6 h (−4.17%; P < 0.05 vs 0). A significant Tg change was observed after 6 h (+70.37%; P < 0.01 vs 0) and 9 h (+58.33%; P < 0.05 vs 0) respectively, and the increase was +22.22% at 3 h and +18.52% at 12 h. Total cholesterol increase was +0.52% after 3 h, +1.04% after 6 h, while after 12 h the decrease was −0.52%. Low-density lipoprotein cholesterol increase was +1.64% after 6 h with a decrease of −0.82% at 9 and 12 h. A significant sICAM-1, hsCRP, and sE-selectin variation was observed after 6 and 9 h, while a significant sVCAM-1 change occurred after 3, 6, and 9 h. Soluble ICAM-1 increase was +20.58% at 3 h, +34.10% at 6 h (P < 0.05 vs 0) +25.94% at 9 h (P < 0.01 vs 0), and +19.14% at 12 h; sVCAM-1 increase was +13.97% (P < 0.05 vs 0) at 3 h, +18.55% at 6 h (P < 0.01 vs 0), +12.02% at 9 h (P < 0.05 vs 0), and +8.70% at 12 h. High-sensitivity CRP increase was +36.36% at 3 h, +90.91% at 6 h (P < 0.01 vs 0), +63.64% at 9 h (P < 0.05 vs 0), and +36.36% at 12 h. Soluble E-selectin increase was +27.11% at 3 h, +51.90% at 6 h (P < 0.05 vs 0), +45.19% at 9 h (P < 0.01 vs 0), and +20.12% at 12 h. Interleukin-6 increase was +61.11% at 3 h (P < 0.05 vs 0), +83.33% at 6 h (P < 0.001 vs 0), +55.56% at 9 h (P < 0.01 vs 0), and +22.22% at 12 h. Tumor necrosis factor-α increase was +42.86% at 3 h (P < 0.05 vs 0), +71.43% at 6 h (P < 0.01 vs 0), (+50.00% at 9 h (P < 0.05 vs 0), and +28.57% at 12 h. We observed that the OFL induces a complex and massive systemic inflammatory response that includes IL-6, TNF-α, hsCRP, and cell adhesion molecules, even before Tg significantly rises."
http://www.springerl...8n32355687p665/

So yes, carbohydrates cause a postprandial inflammation, but so does fat.

Edited by Blue, 21 October 2009 - 04:01 PM.

[tunt01]

So yes, carbohydrates cause a postprandial inflammation, but so does fat.

true. common sense says we should get off our asses and be physically active to blunt the impact.

i think the postprandial impact of carbs (and food in general) is a knock on a sedentary lifestyle, more than carbs itself.

[Johann]

Extremely few people have a diet with so little carbohydrates and protein that they achieve long-term ketosis. So studies regarding a true ketogenic diet, that is producing ketone bodies and not wrongly "ketogenic diet"=reduced carbohydrates, are not relevant for the epidemiological studies.

Then why did you start this thread in the first place? Wasn't it to give the impression that low carb diets are bad?
Ya know, sometimes we have to take things with a grain of salt. And we must realize that there is a money trail involved. The wheat and corn industry can covertly fund checkbook research because they need people eating their wheaties which then helps out the entire medical industry due to increased heart disease and diabetes. Not to mentions the millions of gallons of inflammation causing soybean and corn oil that is consumed every year in the name of Low Cholesterol.
So I don't give two cents for your studies that any body can google and find.

Edited by Johann, 21 October 2009 - 06:06 PM.

[Blue]

So yes, carbohydrates cause a postprandial inflammation, but so does fat.

true. common sense says we should get off our asses and be physically active to blunt the impact.

i think the postprandial impact of carbs (and food in general) is a knock on a sedentary lifestyle, more than carbs itself.

Probably right, this may be less of a problem if you do physical work after a meal which increase nutrient intake. But difficult to do after every meal today, unless you work in occupation requiring physical activity.

[frederickson]

Extremely few people have a diet with so little carbohydrates and protein that they achieve long-term ketosis. So studies regarding a true ketogenic diet, that is producing ketone bodies and not wrongly "ketogenic diet"=reduced carbohydrates, are not relevant for the epidemiological studies.

Then why did you start this thread in the first place? Wasn't it to give the impression that low carb diets are bad?
Ya know, sometimes we have to take things with a grain of salt. And we must realize that there is a money trail involved. The wheat and corn industry can covertly fund checkbook research because they need people eating their wheaties which then helps out the entire medical industry due to increased heart disease and diabetes. Not to mentions the millions of gallons of inflammation causing soybean and corn oil that is consumed every year in the name of Low Cholesterol.
So I don't give two cents for your studies that any body can google and find.

amen, brother. the money trail you outlined is entirely accurate and strongly biases most nutrition research.

per conversation with dr. loren cordain (paleo diet) himself, it is nearly impossible to get funding for large, randomized controlled trials for diets low in carbs and especially grains. who is going to fund them? the nih, usda, etc. who recommend a grain-based diet and are awash in food industry money will not fund such research due to the financial interests involved.

the bottom line is that positive studies of low-grain diets, and lower carbohydrate diets in general, would cost the major players of the food industry tremendous amounts of money and it is difficult to get this work funded. conversely, any study considering the "benefits of whole grains", or anything that supports the food pyramid (a glorified grain/dairy lobby marketing device), will be funded in a heartbeat.

so i agree, one really must take these kind of findings with a huge grain of salt. i think the millions of real-world improvements of body composition, lipid profiles, energy, etc. provide more testament to the virtues of low-carbohydrate, high protein, and nutrient-dense diets than any money-tainted study can seek to disparage.

[tunt01]

http://www.scienceda...91020162237.htm

ketosis improves spinal cord injury outcomes

[Blue]

Extremely few people have a diet with so little carbohydrates and protein that they achieve long-term ketosis. So studies regarding a true ketogenic diet, that is producing ketone bodies and not wrongly "ketogenic diet"=reduced carbohydrates, are not relevant for the epidemiological studies.

Then why did you start this thread in the first place? Wasn't it to give the impression that low carb diets are bad?
Ya know, sometimes we have to take things with a grain of salt. And we must realize that there is a money trail involved. The wheat and corn industry can covertly fund checkbook research because they need people eating their wheaties which then helps out the entire medical industry due to increased heart disease and diabetes. Not to mentions the millions of gallons of inflammation causing soybean and corn oil that is consumed every year in the name of Low Cholesterol.
So I don't give two cents for your studies that any body can google and find.

amen, brother. the money trail you outlined is entirely accurate and strongly biases most nutrition research.

per conversation with dr. loren cordain (paleo diet) himself, it is nearly impossible to get funding for large, randomized controlled trials for diets low in carbs and especially grains. who is going to fund them? the nih, usda, etc. who recommend a grain-based diet and are awash in food industry money will not fund such research due to the financial interests involved.

the bottom line is that positive studies of low-grain diets, and lower carbohydrate diets in general, would cost the major players of the food industry tremendous amounts of money and it is difficult to get this work funded. conversely, any study considering the "benefits of whole grains", or anything that supports the food pyramid (a glorified grain/dairy lobby marketing device), will be funded in a heartbeat.

so i agree, one really must take these kind of findings with a huge grain of salt. i think the millions of real-world improvements of body composition, lipid profiles, energy, etc. provide more testament to the virtues of low-carbohydrate, high protein, and nutrient-dense diets than any money-tainted study can seek to disparage.

Regarding the food industry, the meat, fish, and dairy producing part certainly have a lot of financial resources, probably more than the grain part. Most people likely spend more money on meat and dairy products than on grain products.

[Blue]

There are lots of very low carbohydrate studies with a variety of different diets (high-fat, high-protein, true ketogenic, low grain, etc). Almost all short-term, a few as long as a year.

So we know very little about the long-term effects especially of a true ketogenic diet.

But there is at least one exception. Many children on a true ketogenic diet stop after being free of seizures for a few years. But some continue longer.

"Long-term outcomes of the ketogenic diet in the treatment of epilepsy have not previously been reported. A retrospective chart review of children treated with the ketogenic diet for more than 6 years at the Johns Hopkins Hospital was performed. The response was documented at clinic visits and by telephone contacts; laboratory studies were obtained approximately every 6 to 12 months. Satisfaction and tolerability were assessed by means of a brief parental telephone questionnaire. In all, 28 patients (15 males, 13 females), currently aged 7 to 23 years, were identified. The median baseline seizure frequency per week at diet onset was 630 (range 1-1400). Diet duration ranged from 6 to 12 years; 19 remain on the diet currently. After 6 years or more, 24 children experienced a more than 90% decrease in seizures, and 22 parents reported satisfaction with the diet's efficacy. Ten children were at less than the 10th centile for height at diet initiation; this number increased to 23 at the most recent follow-up (p=0.001). Kidney stones occurred in seven children and skeletal fractures in six. After 6 years or more the mean cholesterol level was 201mg/dl, high-density lipoprotein was 54mg/dl, low-density lipoprotein was 129mg/dl, and triglycerides were 97mg/dl. Efficacy and overall tolerability for children are maintained after prolonged use of the ketogenic diet. However, side effects, such as slowed growth, kidney stones, and fractures, should be monitored closely."
http://www.ncbi.nlm....pubmed/17109786

Edited by Blue, 22 October 2009 - 05:44 PM.

[kismet]

Regarding the food industry, the meat, fish, and dairy producing part certainly have a lot of financial resources, probably more than the grain part. Most people likely spend more money on meat and dairy products than on grain products.

Exactly, but your post lacks the necessary bite to address Johann's very well-known fear mongering and conspiracy theories. Johann, seriously, I fear you are in the pocket of big MeAt and big Dairy and big EgG. Sorry, but we cannot trust you anymore (those who live by the conspiracy theory, shall perish by the conspiracy theory!)

Can anyone send me the meta-analysis? I can only access older issues of JBMR http://www.ncbi.nlm....pubmed/19419322
I'm wondering why actual bicarbonate supplementation shows stronger effects, maybe the dietary meta-analysis is confounded by something.

Jehle S, Zanetti A, Muser J, Hulter H, Krapf R. Partial neutralization of the acidogenic western diet with potassium citrate increases bone mass in postmenopausal women with osteopenia. J Am Soc Nephrol 2006;17:3213–22.
http://jasn.asnjourn...full/17/11/3213
Our observed net lumbar spine BMD increase (1.9%) is large and compares favorably with the month 12 increase of raloxifene (1.7%),
although it is less than for the approved daily dose of ibandronate (3.9% [40,41]). Importantly, our observed changes using
potentially bone-anabolic KCl as comparator may underestimate placebo-controlled efficacy...

Bone. 2009 Jan;44(1):120-4. Epub 2008 Sep 26.
Alkaline mineral water lowers bone resorption even in calcium sufficiency: alkaline mineral water and bone metabolism.
Wynn E, Krieg MA, Aeschlimann JM, Burckhardt P.

Lest anyone forget the hypothesis I proposed some time ago: Kidney stones in ketosis are promoted by a lack of IP6.

Edited by kismet, 22 October 2009 - 05:42 PM.