No one wants to hear it

Ilana_Rose · 2019-07-22 11:38:03 UTC

Not just the data either. The protocols matter immensely. We have no way to know if this is a n=5 experiment, or if the three groups even were examined under similar methods. This might be the best science ever or nothing more than some pulling together of a few elements from various studies to generate a hypothesis that still requires testing. He simply hasn’t told us.

PaulL · 2019-07-22 13:51:55 UTC

Bikman’s study was unpublished at the time the lecture was filmed, but it is now out and available on PubMed. Have a go at it, and tell us what you think.

Katiekate · 2019-07-22 21:59:25 UTC

I went to Pubmed. PubMed is not a publisher … It is just an index to studies…not the studies themselves

Can you tell me where it was published? NewEngland Journal? Metabolic studies journal?

Katiekate · 2019-07-22 22:00:22 UTC

Or…the title of the study?

Katiekate · 2019-07-23 01:18:01 UTC

True…but, consider. Just the fact that your actually were published in a journal of the medical practice you are writing about means that many eyes have scrutinized the work before it ever sees print…the. Once in print many will follow the protocol and attempt to repeat your findings. All of that can be pretty intimidating if you are in any way shaky in your research data, protocol, or QA.

Today is a different world. The world of medicine was nowhere near as advanced in Keys day…nor was his work available world wide like today. There are literally hundreds of researchers pouring thru published works…not like decades before the internet when a significant work could languish for years.

PaulL · 2019-07-23 01:58:17 UTC

@Katiekate You are right; like Google Scholar, PubMed is an index, not a periodical. So let’s see. Here are the papers Prof. Bikman cites during the video linked in post 201 of this thread. All references were displayed in his slides. These are mostly PubMed links, which is half your work done for you. I leave it to you to decide which papers you want to consult, and to find the full texts, if available (if you have a hard time deciphering the journal abbreviations, PubMed provides a list):

ncbi.nlm.nih.gov

Insulin selectively reduces mitochondrial uncoupling in brown adipose tissue in mice.

BW Dallon, BA Parker, AE Hodson, TS Tippetts, ME Harrison, MMA Appiah, JE Witt, JL Gibbs, HM Gray, TM Sant and BT Bikman, The Biochemical journal, 2018 09 02

The purpose of the present study was to determine the effects of prolonged hyperinsulinemia on mitochondrial respiration and uncoupling in distinct adipose tissue depots. Sixteen-week-old male mice were injected daily with placebo or insulin to induce an artificial hyperinsulinemia for 28 days. Following the treatment period, mitochondrial respiration and degree of uncoupling were determined in permeabilized perirenal, inguinal, and interscapular adipose tissue. White adipose tissue (WAT) mitochondria (inguinal and perirenal) respire at substantially lower rates compared with brown adipose tissue (BAT). Insulin treatment resulted in a significant reduction in mitochondrial respiration in inguinal WAT (iWAT) and interscapular BAT (iBAT), but not in perirenal WAT (pWAT). Furthermore, these changes were accompanied by an insulin-induced reduction in UCP-1 (uncoupling protein 1) and PGC-1α in iWAT and iBAT only, but not in pWAT or skeletal muscle. Compared with adipose tissue mitochondria in placebo conditions, adipose tissue from hyperinsulinemic mice manifested a site-specific reduction in mitochondrial respiration probably as a result of reduced uncoupling. These results may help explain weight gain so commonly seen with insulin treatment in type 2 diabetes mellitus.

ncbi.nlm.nih.gov

Effects of glucagon on lipolysis and ketogenesis in normal and diabetic men.

JE Liljenquist, JD Bomboy, SB Lewis, BC Sinclair-Smith, PW Felts, WW Lacy, OB Crofford and GW Liddle, The Journal of clinical investigation, Jan 1974

The effect of glucagon (50 ng/kg/min) on arterial glycerol concentration and net splanchnic production of total ketones and glucose was studied after an overnight fast in four normal and five insulin-dependent diabetic men. Brachial artery and hepatic vein catheters were inserted and splanchnic blood flow determined using indocyanine green. The glucagon infusion resulted in a mean circulating plasma level of 4,420 pg/ml. In the normal subjects, the glucagon infusion resulted in stimulation of insulin secretion indicated by rising levels of immunoreactive insulin and C-peptide immunoreactivity. Arterial glycerol concentration (an index of lipolysis) declined markedly and net splanchnic total ketone production was virtually abolished. In contrast, the diabetic subjects secreted no insulin (no rise in C-peptide immunoreactivity) in response to glucagon. Arterial glycerol and net splanchnic total ketone production in these subjects rose significantly (P=<0.05) when compared with the results in four diabetics who received a saline infusion after undergoing the same catheterization procedure.Net splanchnic glucose production rose markedly during glucagon stimulation in the normals and diabetics despite the marked rise in insulin in the normals. Thus, the same level of circulating insulin which markedly suppressed lipolysis and ketogenesis in the normals failed to inhibit the glucagon-mediated increase in net splanchnic glucose production. It is concluded (a) that glucagon at high concentration is capable of stimulating lipolysis and ketogenesis in insulin-deficient diabetic man; (b) that insulin, mole for mole, has more antilipolytic activity in man than glucagon has lipolytic activity; and (c) that glucagon, on a molar basis, has greater stimulatory activity than insulin has inhibitory activity on hepatic glucose release.

ncbi.nlm.nih.gov

The effects of triglyceride absorption upon glucagon, insulin, and gut glucagon-like immunoreactivity.

I Böttger, R Dobbs, GR Faloona and RH Unger, The Journal of clinical investigation, Oct 1973

The effects of a fat meal upon plasma insulin, glucagon, and glucagon-like immunoreactivity (GLI) have been studied in conscious dogs and in human volunteers. In dogs the intraduodenal instillation of 10 g/kg of peanut oil was accompanied by increases in the mean plasma levels of all three polypeptides that averaged 5 muU/ml, 107 pg/ml, and 2.1 ng/ml, respectively. 3 g/kg of peanut oil, when emulsified with egg yolk, elicited a much greater response of the three hormones, and a physiologic dose of 1 g/kg in emulsified form also caused a significant rise in glucagon and GLI. The islet cell hormone response was not ascribable to chylomicronemia since intravenous infusion of canine chyle failed to stimulate glucagon secretion; moreover, in dogs with a thoracic duct fistula in which chyle was excluded from the circulation, the intraduodenal administration of a fat meal elicited the normal islet cell hormone response, as well as a rise in GLI. 10 g/kg of medium-chain triglycerides failed to elicit these same responses. In six human volunteers the oral administration of 3 g/kg peanut oil was accompanied by increments of 2 muU/ml, 26 pg/ml, and 1.5 ng/ml in the mean levels of insulin, glucagon, and GLI. The changes in insulin and glucagon in man were neither statistically significant nor biologically impressive. It is concluded that in dogs fat absorption is accompanied by prompt and substantial increases in plasma glucagon and GLI and a small transient rise in insulin. The evidence favors an enterogenic signal to the islets of Langerhans rather than their stimulation by chylomicrons. Pancreozymin is qualified to serve as such a signal. The physiologic implications of this study are considered.

ncbi.nlm.nih.gov

The effect of alanine on glucagon secretion.

WA Müller, GR Faloona and RH Unger, The Journal of clinical investigation, Oct 1971

If glucagon plays a hormonal role in the regulation of gluconeogenesis from endogenous amino acids, its secretion might be stimulated by an increase in the concentration of alanine, which has recently been identified as a principal gluconeogenic precursor. To determine if this is the case, 0.75 mmole of alanine per kilo was infused into conscious dogs immediately after a priming injection of 0.25 mmole per kg for 15 min. A uniform rise in the plasma level of pancreatic glucagon, as determined by a relatively specific radioimmunoassay for pancreatic glucagon, was observed. The rise, which averaged 90 pg per ml, was highly significant at 7(1/2) and 15 min after the start of the infusion. Insulin rose an average of only 8 muU per ml, while glucose rose an average of 10 mg per 100 ml. A lower dose of alanine, 1 mmole per kg, infused over a 1 hr period without an initial priming injection, also elicited a significant rise in glucagon measured in the pancreaticoduodenal venous plasma; glucagon rose from 350 pg per ml to 1066 pg per ml at the end of the infusion. The insulin response was modest and inconsistent, and glucose, again, rose 10 mg per 100 ml. To determine if the availability of exogenous glucose would abolish the alanine-induced rise in glucagon secretion, dogs were made hyperglycemic by a constant intravenous glucose infusion and were then given the high-dose alanine infusion. Under these circumstances, glucagon did not rise above the mean fasting concentration of 75 pg per ml, whereas mean insulin rose dramatically by more than 100 muU per ml. It was concluded that, in the fasting state, alanine does stimulate the secretion of glucagon, while having very little stimulatory effect on insulin secretion. Glucagon could, therefore, be a humoral mediator of gluconeogenesis from endogenous alanine, responding to hyperalaninemia in the fasting state, but not when exogenous glucose is available.

ncbi.nlm.nih.gov

Glucagon is essential for adaptive thermogenesis in brown adipose tissue.

K Kinoshita, N Ozaki, Y Takagi, Y Murata, Y Oshida and Y Hayashi, Endocrinology, Sep 2014

Glucagon, a counterregulatory hormone to insulin, serves as a regulator of glucose homeostasis and acts in response to hypoglycemia. Earlier studies have shown that glucagon administration induces thermogenesis in experimental animal models. However, it is not known whether endogenous glucagon is involved in the regulation of brown adipose tissue (BAT) function. Here we investigated the role of glucagon in cold-induced thermogenesis in male mice deficient in proglucagon-derived peptides (GCGKO mice). Upon exposure to cold, GCGKO mice exhibited a greater decrease in rectal temperature than control mice. The cold exposure-induced increase in oxygen consumption in GCGKO mice was less than that seen in control mice. Moreover, the increase in oxygen consumption after administration of a β3-adrenergic receptor agonist, CL-316,243, was also lesser in GCGKO than in control mice. Expression of thermogenic genes, including the gene encoding uncoupling protein 1 (Ucp1), was reduced in the BAT of GCGKO mice under ambient as well as cold conditions. Administration of glucagon restored the expression of Ucp1 mRNA in the BAT as well as the expression of the fibroblast growth factor 21 gene (Fgf21) in the liver. Supplementation with glucagon for 2 weeks resulted in higher plasma Fgf21 levels and improved responses to CL-316,243 in GCGKO mice. These results indicated that endogenous glucagon is essential for adaptive thermogenesis and that it regulates BAT function, most likely by increasing hepatic Fgf21 production.

ncbi.nlm.nih.gov

Insulin and Glucagon: Partners for Life.

JJ Holst, W Holland, J Gromada, Y Lee, RH Unger, H Yan, KW Sloop, TJ Kieffer, N Damond and PL Herrera, Endocrinology, 2017 04 01

In August 2016, several leaders in glucagon biology gathered for the European Association for the Study of Diabetes Hagedorn Workshop in Oxford, England. A key point of discussion focused on the need for basal insulin to allow for the therapeutic benefit of glucagon blockade in the treatment of diabetes. Among the most enlightening experimental results presented were findings from studies in which glucagon receptor-deficient mice were administered streptozotocin to destroy pancreatic β cells or had undergone diphtheria toxin-induced β cell ablation. This article summarizes key features of the discussion as a consensus was reached. Agents that antagonize glucagon may be of great benefit for the treatment of diabetes; however, sufficient levels of basal insulin are required for their therapeutic efficacy.

McGarry et al., “Role of carnitine in hepatic ketogenesis,” Proc. Nat. Acad. Sci., 72:11 (1975), pp. 4385-88

Morton et al., “A systematic review, meta-analysis and meta-regression of the effect of protein supplementation on resistance training-induced gains in muscle mass and strength in healthy adults,” BJSM 52:6 (2018)

There’s no need to thank me; I enjoyed listening to the lecture again.

carolT · 2019-07-23 10:50:37 UTC

Thanks @PaulL ! I know watching Bikman videos is a hardship we impose on you from time to time. Thanks for taking one for the team.

Ilana_Rose · 2019-07-23 11:40:02 UTC

Which is the study that is the crux of it all though? The one where he feeds three human groups. One SAD, one fasting and one 1 g/kg of body weight to show the glucagon to insulin responses. That’s the major finding of his that’s discussed on this forum that is about the reason that we needn’t be concerned with protein amounts on a ketogenic diet.

PaulL · 2019-07-23 11:53:17 UTC

That, padawan, is left as an exercise for the pupil . . .

Seriously, if you search PubMed for “Bikman 2019,” only two studies come up, neither involving people. Apparently the publication of the human arm has been delayed. The McGarry study appears to be rather relevant, however, and might shed some light. Check it out.

Ilana_Rose · 2019-07-23 12:05:34 UTC

I think that’s been @Katiekate’s point though.

I will check it out. Thanks.

amwassil · 2019-07-23 17:09:21 UTC

@KatieMoe You seem to have a high regard for peer review that I no longer share. When a simple google search for “What’s wrong with peer review” turns up 232,000,000 results and a simple NCBI search for “problems peer review” turns up 87684 results, I think there’s ample cause for concern. I think a high degree of skepticism is in order and we need to consider alternatives.

https://www.ncbi.nlm.nih.gov/pmc/?term=problem+peer+review
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1420798/

carolT · 2019-07-23 19:51:55 UTC

Peer review missed a couple of glaring mistakes in this one too. Can you spot any?

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4057547/

ellenor2000 · 2019-07-23 22:53:06 UTC

This is why when trying to do the hard sell on hypercarnivore I say “take it day by day. You can go back to the old ways any time after the first three days, or even within the first three days if the sugar withdrawals are too great. I hope that even if you do, you will refrain from using temperate seed oils (like canola, corn oil, grapeseed oil, soybean oil) in your cooking in the future, instead preferring heat-stable fats like tropical seed oils (coconut, palm kernel), butter, ghee, lard and/or tallow.”

SecondBreakfast · 2019-07-26 18:48:24 UTC

Beef tallow is awesome to cook with. A mix of tallow and butter is awesome.

Regarding no one wants to hear it, though… I’m finding slightly less resistance at times. Letting one’s own results speak for itself seems to have been the way to go. This one co-worker who buys candy and pop for their lunch - has recently started buying protein bars and flavored waters. They won’t say a word, but that has been a new development this week. Another one has started weaning her husband off the carbs, and filling his plate with lo-carb alternatives like the faux-tatoes using cauliflower. He’s a tough nut to crack, but she’s trying - and Im doing what I can to help her.

So, I’m not talking alot about it at all…just letting my incredible shrinking arse do the talking for me.

PaulL · 2019-07-27 18:31:38 UTC

Great film title. Or name for an Indie band.

coffeekittie · 2019-07-27 19:04:51 UTC

Oh wow. I read that as “the incredible stinking arse”. Spit take moment there

Mimi2007 · 2019-08-03 13:43:07 UTC

K.Hellmann · 2019-08-09 12:43:39 UTC

None of my kids will listen to me about Keto, they all keep telling me how dangerous it is, and how I am missing out on so many nutrients and stuff… they will not listen or watch any podcasts

@Momof5 My 5 daughters are the exact same way. They lecture me about being on a fad diet and think I am hurting my heart and health even though I am healthier and more energetic than I’ve been in 10 years. It’s frustrating to say the least.

They are all trying so hard to be healthy and doing all the wrong things and they just keep trying harder without results. I keep staying the course and hoping they will see my results and get curious some day.

Diygurl19 · 2019-08-09 15:14:34 UTC

Eating out is difficult so I do it less and less.

Momof5 · 2019-08-09 17:51:09 UTC

Thanks =) I am doing the same! I have 2 boys (27 and 23) and 3 girls (18,21 and 25). Good luck to us both in being healthy Keto ladies =).