Tuesday, October 28, 2008

Saturated Fats as Potent Anti-Atherogenic Drugs

I hope we are not still scarred by the long onslaught of ingrained sat-fat nonsense over the last few decades?

SCAR TISSUE from Red Hot Chili Peppers
ALBUM: Californication

Courtesy of Youtube.com


In the previous entry, conclusions from the same research below was discussed. They went further and looked at the lipoprotein subfractions including HDL2b and HDL3c. Mensink et al found that the higher the phospholipid transfer protein (PLTP) activity and the lower the cholesterol ester transfer protein (CETP) activity, the higher the relative abundance of HDL2b, the regression particle, and the lower the HDL3c, a small dense atherogenic particle. Lauric acid produced the highest ratio of PLTP to CETP activity when compared with the control, palmitic or oleic diets after 6-weeks.

Their assessment was "It is now clearly established that CETP and PLTP can modulate the size distribution of serum lipoprotein fractions. On the one hand, CETP can replace lipoprotein cholesteryl esters by hydrolyzable triglycerides which are derived from the triglyceride-rich lipoproteins, favoring the emergence of small-sized LDL, pre-beta-HDL and small-sized alpha-HDL [40]. On the otherhand, PLTP has been shown to promote the formation of both pre-beta-HDL and large-sized alpha-HDL through an inter-HDL fusional mechanism [40]. In the present study, no significant differences in the size distribution of either HDL or LDL fractions were observed in sera from subjects consuming either of the three experimental diets... Despite the absence of modifications of the size distribution of HDL, significant relationships between lipid transfer activities andthe relative abundance of HDL subpopulations were observed among (INDIVIDUAL) subjects consuming the same, standardized diet. Overall, CETP correlated positively with small HDL, but negatively with large HDL, whereas opposite tendencies were observed with PLTP that correlated negatively with small HDL, but positively with the large ones (ie, HDL2b)."

  • Variations in serum cholesteryl ester transfer and phospholipid transfer activities in healthy women and men consuming diets enriched in lauric, palmitic or oleic acids. Lagrost L, Mensink RP, Guyard-Dangremont V, Temme EH, Desrumaux C, Athias A, Hornstra G, Gambert P. Atherosclerosis. 1999 Feb;142(2):395-402. Email for PDF.


    Minimization and maximization, respectively, as the Mensink study showed.

    What are the dangers of artificially inhibiting CETP and ignoring PLTP activity?

    What are the dangers of raising only HDL3c (small dense atherogenic HDL) and lowering HDL2b (the regressive, large/fluffy HDL)??!

    The story of Torcetrapib...is one with an extremely unhappy unending...

    Well...for one Pfizer is now out of the lipid-heart-disease business (Lipitor® RIP 2011 when it goes generic). Read the TYP report on this CETP-inhibitor and the surprising outcome HERE. Pfizer's $20B Torcetrapib HDL-raising drug unfortunately failed big time (in low-fat, low cholesterol, low saturated fat populations). Not only was an increase of 50% in total HDL observed in humans but also coronary regression was demonstrated in animal studies. Oddly this curious drug was associated with nearly double the deaths in the single human morbidity/mortality trial. Are animal brains as functional or large as human brains? What is the purpose of cholesterol? Are humans brains not laden with cholesterol? In fact 23% of the whole body pool of cholesterol is found in the brain and central nervous system. Although the brain only weighs 2.1% of our total weight, the cholesterol content is the highest compared with any other tissue (23 mg chol/gram). How much cholesterol is in an egg yolk? A measly ~200 mg. Barely enough to support or maintain a smidgeon of your SUPER SAVANT BRAIN. And we're told to have no more than an egg a day? Can you spell autism? Well... probably neither can the great-grandchildren of the geniuses who proposed these low-cholesterol indictments. How many more generations will be affected by the policies propagating the low-fat hypothesis? Are we de-evolving as a species *hint....WALL*E *?

    Thematic review series: Brain Lipids. Cholesterol metabolism in the central nervous system during early development and in the mature animal. Journal of Lipid Research, Vol. 45, 1375-1397, August 2004.


    Fish oil EPA + DHA and seafood naturally lower CETP activity (preventing cholesterol transfer) and power up PLTP (moving phospholipids out of lipoprotein fractions). I had a hard time locating any VAP/NMR data on effects of fish oil components EPA and DHA, but two studies below demonstrate the outcome of EPA and DHA ingestion in depleting phospholipids out of LDL and HDL particles.

    (1) Small supplements of N-3 fatty acids change serum low density lipoprotein composition by decreasing phospholid and apolipoprotein B concentrations in young adult women. Terpstra AH et al. Eur J Nutr. 1999 Feb;38(1):20-7.

    (2) The effect of dietary n-3 polyunsaturated fatty acids on HDL cholesterol in Chukot residents vs Muscovites.
    Astakhova T et al. Lipids. 1991 Apr;26(4):261-5.
    Native Chukot Peninsula residents, in contrast to Muscovites, consume a diet rich in n-3 polyunsaturated fatty acids. This dietary peculiarity is reflected in differences in plasma lipid and apolipoprotein contents. The Chukot residents have lower contents of total cholesterol, triglyceride, LDL (low density lipoprotein) cholesterol and apolipoprotein B, but higher HDL (high density lipoprotein) cholesterol levels than do Muscovites. The apolipoprotein A-I levels were identical in both groups. A higher HDL cholesterol to apolipoprotein A-I ratio was determined in the coastline Chukot residents (0.52 +/- 0.01) than in Muscovites (0.43 +/- 0.01; p less than 0.01). In contrast to Muscovites, the coastline Chukot residents also had higher n-3 and lower n-6 polyunsaturated fatty acid percentages in plasma and erythrocyte lipids, and lower phosphatidylcholine and higher sphingomyelin or phosphatidylethanolamine levels in HDL2b and HDL3. The higher HDL cholesterol levels in the plasma of the coastline Chukot residents appears to reflect the higher cholesterol-scavenging capacity of their HDL. We conclude from this study that the regular consumption of dietary n-3 polyunsaturated fatty acids by the coastline Chukot residents decreased LDL cholesterol transfer from plasma to peripheral cells, and enhanced cholesterol efflux from cellular membranes toward HDL.


    Nagao K, Yanagita T. Bioactive lipids in metabolic syndrome. Prog Lipid Res. 2008 Mar;47(2):127-46.
    "This review explores the physiological functions and molecular actions of bioactive lipids, such as n-3 polyunsaturated fatty acids, conjugated fatty acids, sterols, medium-chain fatty acids (LIKE SATURATED FAT LAURIC, CAPRIC, CAPROIC, CAPRYLIC ACIDS), diacylglycerols and phospholipids, in the development of metabolic syndrome. Dietary bioactive lipids suppress the accumulation of abdominal adipose tissue and lipids in the liver and serum, and alleviate hypertension and type 2 diabetes through the transcriptional regulation of lipid and glucose metabolism. "


    Fatty acids including saturated fatty acids also bind PUMA-G and HM74 receptors. This is the receptor family that Niacin binds to and exerts its potent abilities to regress plaque (raise HDL2b 200-300%, lower TGs 40-60%) and evoke its anti-inflammatory effects. See Table 1 full list of the range of ketone body and the saturated fatty acids and their relative receptor affinities.

    Taggart A, Waters MG et al. (D)-beta-Hydroxybutyrate inhibits adipocyte lipolysis via the nicotinic acid receptor PUMA-G. J Biol Chem. 2005 Jul 22;280(29):26649-52. Full 'accelerated publication' PDF here.

    Other fatty acids which bind this astounding receptor PUMA-G are in listing of decreasing potency:
    --Hydroxy-butyrate (ketone bodies associated with exercise training and intermittent fasting)
    --Lactate (by-product of anaerobic exercise, strength training, intense exercise like CALIfornication)
    --Acetate (C2), Proprionate (C3)
    --Decanoate (C10) = caprylic acid, a medium chain saturated fatty acid (MC SFA)
    --Heptanoic acid (C7)
    -- Butyrate (C4) = short chain saturated fatty acid from butter oil and produced by gut flora from ingested fiber like oat bran, pectin, etc
    --Octanoate (C8) = capric acid, MC SFA
    --Pentanoic acid (C5)
    --Hexanoate (C6) = caproic acid, MC SFA
    --Nicotinic acid (niacin, SLO-NIACIN, NIASPAN) -- binds with high affinity to HM74 receptors

    dr j said...

    from dr j in oz..
    Gosh G you are a busy beaver,

    Its interesting how one's focus changes. My mother was recently diagnosed with cancer and my focus is trying to find a Dr Davis/Peter/G/TYP for that area..its hard

    There is a crossover point in oils though....through trying to separate useful observations from drivel re Dr Johanna Budwig's flaxseed/cottage cheese mixture. She believed that oil is better handled in the body by first ( my guess) liposoming the oil with sulphur containing proteins from the cottage cheese. These are then "water soluble" and can be better transported to the cells.

    At this point I bring in something that Dr McCleary said that krill oil is preferable to fish oil because it is able to be transported across the blood brain barrier into the grey matter because of the phospho-lipid fraction . To my intuition, there just seems a surfactant connection factor that might be lurking here..

    It is also interesting ( to me ) that my coconut oil inclusion in my diet has lifted my HDL up but my LDL wont go down ( it could be large LDL anyway so who cares). AND and my hb1Ac has lifted from 5.1% on a carbo diet to 5.8% on a 25 gm per day carbo input .

    My mother said that the nurses said I was good looking.. I said , no it was because I bought them a big box of chocolates..haha.

    Here is something useful about niacin from pub med ( I am now using a 1% lipoderm+niacinamide cream for outdoors)

    Oral niacin prevents photocarcinogenesis and photoimmunosuppression in mice.

    Gensler HL

    Arizona Cancer Center, Department of Radiation Oncology, University of Arizona College of Medicine, Tucson 85724, USA.

    Topical nicotinamide (niacinamide) has demonstrable preventive activity against photocarcinogenesis in mice. To better understand how this vitamin prevents ultraviolet (UV) carcinogenesis, we tested systemic administration of another form of the vitamin, niacin, and its capacity to elevate cutaneous nicotinamide-adenine dinucleotide (NAD) content as well as to decrease photoimmunosuppression and photocarcinogenesis. BALB/cAnNTacfBR mice were fed the AIN-76A diet supplemented with 0%, 0.1%, 0.5%, or 1.0% niacin throughout the experiment. UV irradiation consisted of five 30-minute exposures per week to banks of six FS40 Westinghouse sunlamps for 22 weeks in the carcinogenesis experiments, yielding a total cumulative dose of approximately 1.41 x 10(6) Jm-2 of UV-B radiation. Dietary supplementation with 0.1%, 0.5%, or 1.0% niacin reduced the control incidence of skin cancer from 68% to 60%, 48%, and 28%, respectively, at 26.5 weeks after the first UV treatment. Two potential mechanisms by which niacin prevents tumor formation were identified. Photoimmunosuppression, critical for photocarcinogenesis, is measured by a passive transfer assay. Syngeneic, antigenic tumor challenges grew to an average of 91.6 +/- 19.7, 79.8 +/- 11.5, 41.9 +/- 11.7, or 13.2 +/- 4.1 mm2 in naive recipients of splenocytes from UV-irradiated mice treated with 0%, 0.1%, 0.5%, or 1.0% niacin supplementation, respectively, demonstrating niacin prevention of immunosuppression. Niacin supplementation elevated skin NAD content, which is known to modulate the function of DNA strand scission surveillance proteins p53 and poly(ADP-ribose) polymerase, two proteins critical in cellular responses to UV-induced DNA damage. These results clearly demonstrate a dose-dependent preventive effect of oral niacin on photocarcinogenesis and photoimmunosuppression and establish the capacity of oral niacin to elevate skin NAD levels

    Pharmacologic doses of nicotinamide in the treatment of inflammatory skin conditions: a review.

    Niren NM

    University of Pittsburgh Medical Center, Pennsylvania, USA.

    Various skin disorders with an inflammatory component often have been treated with steroids and/or oral antibiotics. However, long-term use of these agents has drawbacks: steroids may induce numerous serious side effects such as hypertension, immunosuppression, and osteoporosis, and overuse of oral antibiotics may contribute to the development of bacterial resistance, as well as to a host of nuisance side effects such as diarrhea, yeast infections, and photosensitivity. As a result, alternative oral treatments, such as nicotinamide, have been investigated. During the past 50 years, many clinical reports have identified nicotinamide as a beneficial agent in the treatment of a variety of inflammatory skin disorders; what's more, its exceptional safety profile at pharmacologic doses makes it a potentially ideal long-term oral therapy for patients with inflammatory skin diseases. A recent large study evaluating nicotinamide for the treatment of acne or rosacea has confirmed the potential benefits of oral nicotinamide as an alternative approach to managing inflammatory lesions associated with acne vulgaris and acne rosacea. This article reviews the substantial number of reports published over the past 50 years that document the clinical utility and safety of oral and topical formulations of nicotinamide for the treatment of a variety of inflammatory skin conditions.

    UV radiation-induced immunosuppression is greater in men and prevented by topical nicotinamide.

    Damian DL

    Department of Dermatology, Melanoma and Skin Cancer Research Institute, Sydney Cancer Centre, University of Sydney, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia. diona.damian@email.cs.nsw.gov.au

    UV radiation-induced immunosuppression augments cutaneous carcinogenesis. The incidence of skin cancer continues to increase despite increased use of sunscreens, which are less effective at preventing immunosuppression than sunburn. Using the Mantoux reaction as a model of skin immunity, we investigated the effects of solar-simulated (ss) UV and its component UVA and UVB wavebands and tested the ability of topical nicotinamide to protect from UV-induced immunosuppression. Healthy, Mantoux-positive volunteers were UV-irradiated on their backs, with 5% nicotinamide or vehicle applied to different sites in a randomized, double-blinded manner. Subsequent Mantoux testing at irradiated and adjacent unirradiated sites enabled measurement of UV-induced immunosuppression with and without nicotinamide. Suberythemal ssUV caused significant immunosuppression, although component UVB and UVA doses delivered independently did not. Men were immunosuppressed by ssUV doses three times lower than those required to immunosuppress women. This may be an important cause of the higher skin cancer incidence and mortality observed in men. Topical nicotinamide prevented immunosuppression, with gene chip microarrays suggesting that the mechanisms of protection may include alterations in complement, energy metabolism and apoptosis pathways. Nicotinamide is a safe and inexpensive compound that could be added to sunscreens or after-sun lotions to improve protection from immunosuppression. immunosuppression.


    Dr. B G said...

    Hi dr j,

    I think you're totally right -- there is a crossover point. The liposome theory does make a lot of sense. Drug delivery systems are relevant. Personally fish oil+astaxanthin prevents me from sliding into autism *wink*. Krill might be better...Didn't we talk about this in the past?? ha haaa ha (that's u?)

    LDL can be lowered by fiber, veggies, taurine, protein, CLA/butter oil -- don't worry if it's less than 100 mg/dl. I don't know if the higher glucoses mean anything in the context of low insulins.

    I'm very very sorry to hear about your mum. Here are two websites that I've found immensely helpful for cancer patients (all types). (I had another -- which I can't locate).

    Jefferson in Philly (Philadelphia PA) Myrna Brind protocols -- I believe there is a WAP connection...

    high dose vit D (blood 25OHD = 75 ng/ml)
    high dose vit A (25,000 IU or higher/day for 6-12mos)
    ultra HIGH dose fish oil (4-20 g/day of 50% omega-3 content = what we use 10g/day), mushrooms
    antioxidants (mitochondrial rejuvenators): carnitine, lipoic acid, boswellia, curcumin, coenzyme Q10, etc.
    stress reduction

    Everything TYP is also cancer regressive -- when I look in Pubmed for what we use and employ, cancer regimens and experiments constantly pop up:
    --cruciferous veggies
    --low carb/ketosis/intermittent fasting
    --wheat and grain elimination (no corn, barley, rye)
    --no dairy, no legumes
    --stress reduction, vitamin 'O'
    --GLA (borage oil), nuts, olive oil, coconut oil, MCT oil, butter oil, CLA, etc
    --magnesium, pycnogenol, arginine, taurine, lysine/proline, citrulline, leucine (BCAA), vitamin C, B-complex, vitamin E, K1 K2, carotenoids -- krill oil, astaxanthin, etc

    Cholesterol Myth

    Great info about cancer (and CAD/longevity) protective effects from NIACIN from Rich/California.

    THANKS for the niacin links... Your mum is a lucky to gal to have such a considerate, thoughtful man. Stay strong...


    Anonymous said...

    This is great research and information. But the real question is: can we support the protein and fat requirements that are being put forward for the current world population?
    Is grassfed beef a luxury or a possibilty?
    Or are we facing a future of science fiction protein? And fat?
    The tide appears to be changing in dietary preferences in the US, albeit slowly. But at some point, more people will start demanding more protein/fat. What happens then.

    Dr. B G said...


    We're voting for a bill that allows chickens and animals to walk around and spread their wings. Yes we have to legalize the rights of PHARM ANIMALS. Consequently, the prices will be driven up for grocery store and Costco meat... Hopefully, eventually the tides will shift and more demand for local, sustainable protein/fat will be balanced back into the equation. Green Pastures my raw milk/butter supplier (who I see delivering every Tue to the health food store I patronize) is being shut down by dairy 'industry'... isn't that the saddest thing you've ever heard?

    Protein/fat? I'm actually more worried about our water resources...

    Anonymous said...

    dr. b g,

    Which is more effective in reducing lp(a), which I have, virgin Coconut Oil or MCT oil? Also, do they differ in how they impact small LDL, which I also have?

    I notice that the Coconut Oil is almost 50% Lauric Acid plus lesser amounts of Myristic Acid, Caprylic Acid, Capric Acid, Oleic Acid, and Linoleic Acid. MCT Oil is exclusively Caprylic Acid and Capric Acid.


    Dr. B G said...


    I've wondered too! There actually is an article showing that saturated medium chain fats will act as ANTAGONISTS of PPAR (increasing LDL particle count and lower HDL) if in the presence of cortisol and other hormones (hyperinsulinemia) etc.

    MCT oil seems to me the concentrated amounts of the active ingredient of coconut oil. It's a little more expensive of course as well. Let me know how it works for you! I'll have a little experiment going on soon too...