Monthly Archives: February 2013

What Causes Acne? An Overview

I’ve been promising a series on acne and rosacea for almost two years, but I’ve had trouble working up enthusiasm for it. The problem is that Pubmed has 12,966 papers on acne and 2,587 papers on rosacea, most of those papers are of poor quality, and it is painful to sift through the dross in search of gold.

Fortunately, Seppo Puusa, who blogs at the Acne Einstein, has offered to help. Seppo’s a very smart guy and I thought a conversation between us about acne and rosacea might be an interesting way to do the series.  Seppo has just written a book called Clear for Life: Science-Based Natural Acne Treatment Program, which looks like a terrific guide to overcoming acne. In this first post in our acne and rosacea series, Seppo gives us his overview of acne. Here’s Seppo!

Does it ever feel like acne is just maddeningly confusing? That it just comes and goes without making any sense? It’s almost as if acne is not one disease but a combination of many diseases. For example one person gets acne from eating gluten, while another claims she can eat whatever she wants but breaks out every time she uses certain skin care products. A third person puts the blame on stress. Another person said zinc supplements helped her to get clear.

Is there a way to make sense of this, to reconcile all these seemingly separate causes? I believe there is. And in this post I’ll do my best to give you a framework for understanding acne. Something that ties all these seemingly separate causes together and helps you to make sense of your acne.

Deconstructing acne

In Tim Ferris’s latest book The Four Hour Chef he explains how to use deconstruction to learn a new skill. Basically you boil the skill down to its bare essentials. In acne these are inflammation and hormones (insulin to be more specific).

Let me start by explaining the pimple formation process. Looking at what happens in your skin is important because, surprisingly, understanding this helps you to understand how diet, gut issues, stress and other things can cause acne. Acne is more than skin-deep, but it still happens at the skin.

In acne, skin cells produce too much keratin, a protein that’s the key structural component of your skin, hair and nails. In the skin it holds skin cells together. Normally as skin cells die they separate and are pushed out of the hair/skin follicle (I’ll just call this a “skin pore” from now on). But the excess keratin makes it harder for the dead cells to separate so they are shed in larger lumps. [1]

These lumps of dead skin cells can block the skin pore, and this block prevents sebum from flowing out. One study showed that acne-prone skin produces about 3 times more sebum than normal skin [2], though other studies have found somewhat smaller differences [3, 4]. Now this torrent of sebum flows into the blocked pore and has nowhere to go. So the skin pore expands, like what happens when you blow into a balloon. Oxygen content drops in the blocked pore, and this helps the bacterium P. Acnes to thrive in the blocked pore [5]. The rest you probably know: the immune system responds and causes inflammation in the area.

This process has two breakpoints — points at which we can intervene to prevent or lessen acne. These are:

  • Excess keratin production
  • Excess sebum production

Counter either, or both, of these and your chances of getting acne go down dramatically. And here is where inflammation and hormones comes into play. Because research shows that inflammation in the skin and hormonal factors are the key drivers in both excessive keratin and sebum production.


Many people think of acne as bacterial disease, but more than anything it’s an inflammatory problem. Many researchers now believe that inflammation in the skin is the trigger that kicks off the whole process. Studies have shown that inflammation is present in the very earliest stages of a pimple, even before P. Acnes bacteria colonizes the skin pore [6, 7]. Cell culture studies also show that inflammatory cytokines increase both sebum and keratin production [1,8]. Finally, several studies have shown that antioxidants, whether topical and supplemental, can be as effective as benzoyl peroxide or antibiotics in treating acne [5,9]; this is consistent with the inflammatory view because oxidative stress can trigger inflammation.


Acne has been conclusively linked to elevated levels of androgens, insulin, and insulin like growth factor 1 (IGF-1). These hormones stimulate sebum production and there’s some research to suggest they also affect keratin production. [1]

The relationship between acne and hormones is quite complicated. Androgens, or male sex hormones, are arguably the primary hormones affecting the skin. It has been shown that acne does not occur in people with inactive androgen receptors in the skin [10].

However, acne patients do not necessarily have higher levels of androgen hormones than people with clear skin. A portion of acne patients seem to have higher levels of some androgen hormones, but this is far from universal. Rather, acne-prone skin seems to be excessively sensitive to androgen hormones.

Insulin and IGF-1 are key hormones in acne. That’s because while androgens mediate lot of the effects on the skin, insulin and IGF-1 are the hormones you have the most control over. I like to call insulin a booster hormone in acne. And where there’s insulin, there’s also IGF-1. That’s why I group these two hormones together. [11]

Insulin and IGF-1 can stimulate sebum production on their own, but they also stimulate the release of androgen hormones from the liver and can increase the skin’s sensitivity to androgen hormones. That’s why studies show low GI diets can help with acne, and why milk can be so bad for the skin. [1, 11]

How sebum production drives antioxidant demand

The skin is the most exposed of all the organs. It’s frequently exposed to UV radiation, ozone from air pollution, bacteria, dust and other ‘inflammatory insults’. So the skin needs constant protection, and that protection comes in the form of antioxidants. In the skin the antioxidants are primarily in sebum. [12]

Research shows a tight correlation between sebum production and vitamin E secretion by the skin [13]. More specifically vitamin E secretion correlates with squalene secretion. Squalene is a fatty acid and a part of sebum. It really looks like the body uses vitamin E to protect squalene in the skin. When squalene oxidizes it turns into squalene peroxide, a highly inflammatory and comedogenic fatty acid. Animal studies show that applying squalene peroxide on the skin causes acne, and the severity of acne is linked to the degree of oxidation of squalene [5].

So the more sebum your skin produces the more antioxidants it requires. There’s good evidence to show that the antioxidant system in acne patients just can’t cope up with this increased demand. For example comparing skin and blood levels of several antioxidants shows significantly lower levels in acne patients than in people with healthy skin. [5, 9]

This is the factor that, I believe, ties together all those seemingly disparate factors that can trigger or relieve acne:

  • Gut problems increase systemic inflammation and deplete antioxidant reserves leading to more acne.
  • Stress triggers the release of neurotransmitters (such as substance P) that can increase inflammation in the skin leading to more acne [1].
  • Diet can induce or relieve inflammation leading to more or less acne. Diet also affects insulin levels.
  • Supplementing with zinc or other nutrients can provide antioxidants which lessen acne [14].
  • Candida and other pathogens in the skin cause local inflammation which can induce acne.


Acne is a very complicated condition and I don’t for one second pretend that this simple framework perfectly explains every case. Individual differences exist, and things get much more complicated when we get down into details. But I do believe it’s a good big picture overview of what causes acne and hopefully clears some confusion surrounding it.

Most importantly, this framework is broadly actionable. It gives you a systematic way to approach acne. Anything you can do to lower insulin and inflammation (both systemic and local in the skin) can help in acne.

Just remember, where there’s insulin there’s oily skin, and where there’s inflammation there’s acne.


  1. Ichiro Kurokawa, et al. New developments in our understanding of acne pathogenesis and treatment. Experimental Dermatology. Volume 18, Issue 10, pages 821–832, October 2009.
  2. Harris HH, et al. Sustainable rates of sebum secretion in acne patients and matched normal control subjects. J Am Acad Dermatol. 1983 Feb;8(2):200-3.
  3. S-W. Youn, et al. Does facial sebum excretion really affect the development of acne? British Journal of Dermatology. Volume 153, Issue 5, pages 919–924, November 2005.
  4. Apostolos Pappas, et al. Sebum analysis of individuals with and without acne. Dermatoendocrinol. 2009 May-Jun; 1(3): 157–161.
  5. Whitney P Bowe, Alan C Logan. Clinical implications of lipid peroxidation in acne vulgaris: old wine in new bottles. Lipids in Health and Disease 2010, 9:141.
  6. Eady E, et al. Is Acne an Infection of Blocked Pilosebaceous Follicles?: Implications for Antimicrobial Treatment. American Journal of Clinical Dermatology. July/August 2000 – Volume 1 – Issue 4 – pp 201-209.
  7. Anthony HT Jeremy, et al. Inflammatory Events Are Involved in Acne Lesion Initiation. Journal of Investigative Dermatology (2003) 121, 20–27; doi:10.1046/j.1523-1747.2003.12321.x.
  8. Monica Ottaviani, et al. Lipid Mediators in Acne. Mediators Inflamm. 2010; 2010: 858176.
  9. Bowe WP, et al. Acne vulgaris: the role of oxidative stress and the potential therapeutic value of local and systemic antioxidants. J Drugs Dermatol. 2012 Jun;11(6):742-6.
  10. J Imperato-McGinley, et al. The androgen control of sebum production. Studies of subjects with dihydrotestosterone deficiency and complete androgen insensitivity. The Journal of Clinical Endocrinology & Metabolism February 1, 1993 vol. 76 no. 2 524-528.
  11. Melnik BC, Schmitz G. Role of insulin, insulin-like growth factor-1, hyperglycaemic food and milk consumption in the pathogenesis of acne vulgaris. Exp Dermatol. 2009 Oct;18(10):833-41. Epub 2009 Aug 25.
  12. Jens J. Thiele, Swarna Ekanayake-Mudiyanselage. Vitamin E in human skin: Organ-specific physiology and considerations for its use in dermatology. Molecular Aspects of Medicine. Volume 28, Issues 5–6, October–December 2007, Pages 646–667.
  13. Mauro Picardo, et al. Sebaceous gland lipids. Dermatoendocrinol. 2009 Mar-Apr; 1(2): 68–71.
  14. Dreno B, et al. Multicenter Randomized Comparative Double-Blind Controlled Clinical Trial of the Safety and Efficacy of Zinc Gluconate versus Minocycline Hydrochloride in the Treatment of Inflammatory Acne vulgaris. Dermatology 2001, Vol. 203, No. 2

Around the Web: A New Podcast and Bacterial Warfare

I apologize: I’ve fallen about three weeks behind in responding to the Q&A thread, as I’ve been trying to catch up on other work. I will try to get to all the old questions.

[1] New Podcast with Jonathan Bailor: I had the pleasure of recording a conversation with Jonathan Bailor, producer of The Smarter Science of Slim. I mentioned Jonathan’s new “Slim is Simple” video in my last Around the Web, but there’s more: he’s a terrific conversation partner and his podcast looks to be a great new entry among the leading Paleo podcasts. Check it out!

[2] Help Scholars Understand the Ancestral Health Movement: Historian Hamilton Stapell, who is active in the Ancestral Health Society, is researching the composition of the ancestral health movement. We’re making history, let’s help the historians understand what we’re doing. Please spend a few minutes to fill out his survey.

[3] Music to View Los Angeles By: Via Meredith Harbour Yetter on Facebook, Wilco does “California Stars”:

[4] Interesting Items:

If you’re looking for a new tumblr blog, try WTF, Evolution?.

If you’re looking for a familiar and funny one, re-visit What Should We Call Paleo Life.

MarksDailyApple found this article on barefoot horses doing well in competition. This sentence caught my eye: “Barefoot horses also need to have the sugar levels in their diet carefully managed.” Did horses need shoes because high-carb diets made their feet tender?

Brain cancer mortality increases with Toxoplasma gondii seroprevalence.

More evidence that a high-fat diet promotes longevity: Polish centenarians have high adiponectin.

Emily Deans presents more reasons to eat egg yolks, especially in pregnancy.

Via Dennis Mangan, more evidence that a high-fat diet is good for you: 41% fat is better for mood than 25% fat.

When trees die, humans do too.

Jack Peterson offers advice for undergraduate eating; and he’s interviewed a man who normally does the interviewing, Abel James.

Ray Medina approves of Bifidobacterium infantis.

The food reward idea is in the popular press; a journalist has written a new book on it, Salt Sugar Fat: How the Food Giants Hooked Us that is at #78 at Amazon.

Can you tell the profs from the hobos? (Via Craig Newmark)

Sustainable safe starches: Indian farmers are setting record yields growing rice and potatoes with a technique called System of Root Intensification (SRI), invented by a French Jesuit priest in Madagascar in the 1980s. However, a Chinese scientist questions the yield data.

Hitler was a vegetarian, he planned to convert Germany to vegetarianism after the war, and the Hitler Youth promoted soybeans by calling them Nazi beans. I’ll have to remember that name.

Coca-Cola – 10 liters a day of it – has been linked to a death.

Horsemeat is catching on in England.

Fish is better than fish oil: ProfDr Andro says phospholipid-borne omega-3s are better than triglyceride-borne omega-3s.

Lara Briden, N.D., suggests “gentle carbs” (similar to safe starches) for adrenal health.

Seth Roberts comments on a case in which arthritis was cured by dietary changes that successfully remodeled the gut flora.

Ned Kock wonders if testosterone levels are driven by cortisol.

Finally, orthorexia has become a hot topic on Broadway:

[5] Cute Animals:

Via Yves Smith.

[6] Bacterial Warfare: Here is an interesting video from the current issue of Cell. You may have heard that “tit-for-tat” is a successful strategy in repeated prisoner’s dilemma games – a type of game that resembles microbial competition in the human gut. Microbiologist John Mekalanos and colleagues observed the conditions under which microbes like Vibrio cholerae (whose more virulent strains cause diarrhea and cholera) and Pseudomonas aeruginosa (which is pathogenic in people with cystic fibrosis) choose to fight or co-exist with one another. Listen to Dr. Mekalanos explain bacterial warfare conducted with Type VI secretion systems:

For more, see “Bacterial Battlefield.”

By the way, Shou-Ching is currently working on a video paper showing how tumor cells interact with and attempt to take control of endothelial cells when they are co-cultured. If the paper is open-access, we’ll share her videos when the paper comes out.

[7] Silly Video: If animals had an epidemic that inflated them like beach balls, the Serengeti might look something like this:

[8] S*** Paleo People Say: PaleoFX is a month away, and I’m sure it will be just as fun as this video:

[9] Video of the Week: Lee Saxby discusses how to avoid injuries when running:

Paleolithic Cuisine: How Gourmet Was It?

The Perfect Health Diet is based on biological evidence for what it is healthiest for humans to eat, not on mimickry of Paleolithic diets. Nevertheless, we believe our diet is a pretty good representation of what Paleolithic hunter-gatherers ate – in fact, a better representation than conventional “Paleo.”

We also frequently note that our diet resembles gourmet cuisines. Julia Child would have loved PHD food!

(Hat tip: Cheeseslave)

So does this mean Paleolithic humans were eating gourmet food?

It sounds unlikely. Modern hunter-gatherers tend to eat similar foods day after day, often prepared simply. Lacking supermarkets, it is difficult for them to gather ingredients; lacking refrigeration, they often have to eat food soon after it is obtained; lacking kitchens and equipment, many cooking techniques were not available to them.

But in many ways Paleolithic food may have been quite a bit more Julia Child-like than anthropologists suppose.

Delicious Macronutrient Ratios

In the book, we argue that:

  • The most healthful macronutrient mix is about 30% carb 15% protein 55% fat, with over 90% of the fats saturated or monounsaturated.
  • This healthful mix of macronutrients is also the most delicious, because the reward system of the brain evolved to encourage us to eat healthful food.
  • Paleolithic humans usually succeeded in approaching this optimal macronutrient mix. The Paleolithic diet was typically minority-carb – 15-20% carb much of the time with excursions toward 50% during periods of carb availability – and minority protein – generally 15-30% – and therefore roughly half fat by calories.

Paleolithic food may have been simple, but it had the most delicious mix of macronutrients.

That Paleolithic diets were rich in fat is supported by the observation that hunter-gatherers have always striven for a high fat-to-protein ratio in their diet. Here is anthropologist John Speth:

Inuit diet was actually composed primarily of fat, not lean meat, with the protein contribution seldom surpassing about 35 per cent of their calories, and usually lower, closer to 25 per cent. Pemmican, the traditional mainstay of Native Americans and First Nation peoples (‘Indians’) inhabiting the Great Plains of mid-continental North America, was a mixture of rendered fat and dried, pulverized lean meat, the mix carefully prepared so that the protein component did not exceed 25–30 per cent of total energy (eg, Stefansson 1956; Speth 2010). [1]

Classic gourmet cuisines also generally have this fat-rich macronutrient mix. Classic French cuisine, for instance, is notably rich in saturated fat. This has influenced everyday French eating in a healthful direction, as Wikipedia notes in its discussion of the “French paradox”:

In 2002, the average French person consumed 108 grams per day of fat from animal sources, while the average American consumed only 72 grams. The French eat four times as much butter, 60 percent more cheese and nearly three times as much pork. Although the French consume only slightly more total fat (171 g/d vs 157 g/d), they consume much more saturated fat because Americans consume a much larger proportion of fat in the form of vegetable oil, with most of that being soybean oil. However, according to data from the British Heart Foundation, in 1999, rates of death from coronary heart disease among males aged 35–74 years were 115 per 100,000 people in the U.S. but only 83 per 100,000 in France.

French cuisine is famously delicious. The resemblance of the macronutrient proportions in French cuisine and Paleolithic food suggest that the Paleolithic wasn’t a time of dreary food.

Delicious Plant, Herb, and Spice Combinations

Paleolithic hunter-gatherers ate a much wider variety of plant foods than we do. Gordon Hillman found archaeological residues from 157 plant species at the village of the Paleolithic hunter-gatherers at Abu Hureyra, Syria, and believed that at least another hundred species must have been eaten that left no residues. (Source: note 15 of chapter 24 of our book.) Modern Americans, in contrast, typically confine themselves to about 30 plant species.

So it’s fair to say that Paleolithic cuisine had a much richer variety of plant foods, herbs, and spices than modern cuisines. Paleolithic humans were intimately familiar with their natural environment, and made full use of the diverse foods available to them.

Likewise, hunter-gatherers ate a much wider range of animal organs and tissues than modern Americans, and probably a wider range of fish and animals too. They must have been familiar with a great diversity of ingredients.

What about flavor combinations? Evidence is sparse on this point, but as far back as we have archaeological evidence, we find that foods were combined in tasty ways.

Via John Hawks, I learned of a story in Slate (The Mystery of Curry) that reported the discovery of residues of a ginger, garlic, and turmeric curry from an ancient cooking pot of the Indus civilization. The sub-head of the story: “It turns out we’ve been eating the spiced dish [curry] for a lot longer than anyone ever imagined.”

Paleolithic Cooking Techniques

If Paleolithic humans had access to a great variety of foods and combined them in delicious proportions and flavor combinations, the last obstacle to the Paleolithic Julia Child would have been cooking methods. What cooking technologies did she have?

Fire has been under human control for a long time – the first known use of fire was a million years ago, and fire for heating and cooking was in routine use by 300,000 to 400,000 years ago; heat treatment of tools is known to have been practiced 164,000 years ago (for sources see the discussion in Chapter 2 of the book).

Roasting and broiling on hot coals or stones heated in a fire was undoubtedly the first Paleolithic cooking technology. Cooking in earthen ovens was routine among Native Americans [3] and probably was a Paleolithic technology.

But boiling is more controversial. Ceramic pots were invented only fairly recently, about 20,000 years ago in China and were not used in western Eurasia until the Neolithic. Steam-cracked rocks, a sign that fire-heated rocks were being used to boil water, were not common in Europe until about 25,000 years ago.

Yet archaic humans seem to have been boiling foods long before 25,000 years ago. Neanderthals were boiling their starches at least 46,000 years ago [2], and Speth has argued that to survive at northern latitudes, they must have been obtaining fat from boiled animal bones 200,000 years ago.

So how did they boil without fire-safe pots? Speth again:

Boiling can in fact be done quite effectively without fireproof containers or heated stones. I first became aware of this possibility … [from] an episode of ‘Survivorman’ on the Discovery Channel (2008, Season 2, Episode 4, Part 3, Day 3, African Plains), a program in which wilderness survival expert Les Stroud had to use his wits to stay alive and functioning for several days, alone, in the bush, having with him only the cameras needed to record his daily activities and a very minimal assortment of modern items that he either brought with him or found along the way. He had to improvise almost everything. What caught my attention on that particular occasion was that Stroud had decided to boil water, but the only container he had was a plastic water bottle. To my utter astonishment, he filled it with water, suspended it over an open fire with the bottle squarely in contact with the flames, and proceeded to bring the contents to a rolling boil without destroying the container, noting in passing that so long as the portion of the bottle that came in contact with the flames was filled with liquid the bottle would not burn. [1]

Here is a re-enactment of Stroud’s demonstration on Youtube:

Speth notes that the Ojibwa commonly boiled water and cooked in birch bark baskets, and states, “Direct boiling over an open fire in perishable containers made from paunches, skins, or birch bark – without the use of heated stones – seems to have been a fairly common practice in the temperate and northern latitudes of North America, as amply documented by Driver and Massey (1957:229–231).” [1]

Herodotus, too, noted that the Scythians commonly boiled meaty stews in paunches, with fatty animal bones supplying fuel for the fire when wood was unavailable. In east and southeast Asia and Melanesia, bamboo tubes were the most popular choice for boiling water and steaming rice.

If Paleolithic chefs didn’t bother to invent pottery, perhaps it’s because it wasn’t superior to their hides, bark, and bamboo:

Experiments conducted by Margaret Holman and Kathryn Egan (1985; see also Munson 1989) … [showed that] direct heating with the tray-like bark vessels required substantially less fuel and less time than applying heat indirectly by stone-boiling … [and] also showed that producing syrup in flat-bottomed bark containers was only marginally less efficient in time and labour than using a metal kettle. [1]

From Speth’s perspective, the invention of pottery and stone heating probably signified the increased use of slow-cooking methods such as simmering, not any dramatic change in how food was prepared. [1]

What about frying? If Paleolithic chefs were using hides as pots for boiling, could they have used the same hides to hold fat for frying?

Leather ignites at 210ºC / 410ºF – a warm enough temperature to support frying. Hides can be tanned using vegetable compounds or brains, both materials available to Paleolithic man. I suspect that frying was, if not an everyday technology, certainly a technology that more sophisticated Paleolithic chefs would have experimented with.


It looks like Paleolithic chefs employed a variety of cooking methods – roasting, broiling, boiling, baking, and possibly even frying at temperatures up to 210ºC / 410ºF – and had regular access to a variety of foodstuffs which they were able to combine in the most delicious proportions and flavor combinations. They had, in other words, the ingredients, knowledge, and technology to engage in gourmet cooking.

It’s sad that writing was not invented earlier. We have forever lost the lore of the Paleolithic Julia Child who 50,000 years ago might have written Mastering the Art of Neanderthal Cooking!


[1] Speth JD. Middle Paleolithic subsistence in the Near East: zooarchaeological perspectives – past, present and future. Before Farming 2012(2): 1. Hat tip John Hawks and Melissa McEwen.

[2] Henry A, Brooks A & Piperno D. Microfossils in calculus demonstrate consumption of plants and cooked foods in Neanderthal diets (Shanidar III, Iraq; Spy I and II, Belgium) Proceedings of the National Academy of Sciences, 108 (2), 486-491. See also Henry A, Brooks A & Piperno D. (2011) Reply to Collins and Copeland: Spontaneous gelatinization not supported by evidence Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.1104199108. Hat tip Julien Salvatore.

[3] Kroeber, AL 1925. Handbook of the Indians of California. Bureau of American Ethnology Bulletin 78. Washington, DC: Smithsonian Institution. Cited in [1].

Three New Podcasts

Several podcast interviews have come out this week:

They were all fun to do, I hope you enjoy them!